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ARTES VLP-based vaccine development
As a biopharmaceutical contract research & development organization (CRDO), ARTES Biotechnology has specific expertise in vaccine process development from microbial expression systems. The company offers two versatile and proven virus-like particle (VLP) platform technologies platforms for the development of vaccine candidates. The resulting virus like particles (VLPs) from cell lines are applicable as highly immunogenic subunit vaccines in human and animal health.
METAVAX® is the preferred platform for the development of vaccines with enveloped virus like particle (eVLP) nanostructures.
The second platform, SplitCore, is the technology of choice where capsid virus like particles (cVLPs) are to be applied as antigen presentation vehicles.
Virus-like particles are highly organized protein structures that mimic the conformation of authentic native viruses without being infectious. They consist of one or more structural proteins that have the ability to self-assemble to mimic the structure of real viruses and to present foreign epitopes or complete antigens on their surface.
Because they lack a viral genome, recombinant VLPs are superior to native viruses while at the same time maintaining the same potential to trigger a strong immune response.
Using VLPs to produce prophylactic vaccines is still a leading-edge science with only a few VLP-based vaccines brought to market so far and some others in clinical trials or undergoing preclinical evaluation.
VLP production may take advantage of several established expression systems, including bacterial, yeast, insect and mammalian cells. The choice of ideal production system depends on factors such as cost, ease of expression, ability to scale-up and the need for post-translational modifications (PTMs) that are important in generating optimal immune response.
In addition to the choice of the optimal production cell line, another main challenge of bringing VLP vaccines into production is the design of a cost efficient, scalable and simple downstream process.
ARTES VLP vaccine platforms
Biopharmaceutical process development at ARTES typically starts with the generation of high yield production cell lines based on proprietary yeast expression platform or on E. coli. For the purposes of VLP vaccine development, two different kind of VLP platforms are available at ARTES.
METAVAX®: development of enveloped VLP
METAVAX® is ARTES’ platform technology for vaccine development presenting antigens on the surface of virus like particles (VLP), using the duck hepatitis B virus as scaffold for VLP production.
The resulting chimeric VLP enhance recognition and uptake by antigen presenting cells and result in a potent immune response against the target antigen.
ARTES combines this platform with the WHO-recommended yeast organism Hansenula polymorpha for the development of safe, efficient and affordable vaccines. Animal health vaccines benefit from this antibiotic resistance free platform.
METAVAX® has been applied in several client projects as well as in several in-house research projects.
In a recent study, malaria antigens were fused successfully to dHBsAg resulting in yeast-based eVLPs triggering a transmission blocking immune response.
SplitCore: development of capsid VLP
SplitCore is based on a technology that splits the core or capsid protein of Hepatitis B virus into two parts. These splitted core antigens still form efficiently nanoparticles known as capsid virus like particles (cVLP). On the surface of those particles, differently structured proteins can be added with a high degree of freedom and will then be presented highly exposed and hence effective to the immune system. As expression host yeast or E. coli can be used.
In a recent study, a Borrelia burgdorferi outer surface protein (Lyme disease antigen) was fused successfully to HBc SplitCore for expression in Escherichia coli (E. coli) and self-assembly into capsid VLPs.
Two successful complementary approaches
With SplitCore and METAVAX®, ARTES has two excellent tools available to engineer effective, safe and affordable vaccines based on enveloped and/or capsid VLP nanoparticle technology.
This is in line with ARTES’ proven and successful strategy of offering ‘Plug and Play’ technologies for the development of recombinant protein production.
The next and important part in the development of an affordable vaccine candidate is the development of the production process.
ARTES performs the development and optimization of the fermentation process to ensure low-cost manufacturing with optimal productivity from full synthetic media without animal-derived components or other expensive additives.
Development of the specific VLP purification process benefits from ARTES´ experience with the processes for commercial HepB and HPV vaccine manufacturing.